Composition for enhanced uptake of polar drugs from the colon

Abstract

The invention provides a drug delivery composition for colonic delivery comprising a polar drug, an absorption promoter which (a) comprises a mixture of a fatty acid having 6 to 16 carbon atoms or a salt thereof and a dispersing agent, or (b) comprises a mixture of mono/diglycerides of medium chain fatty acids and a dispersing agent, and means adapted to release the polar drug and absorption promoter in the colon following oral administration. A preferred fatty acid is capric acid or a salt thereof. Colon specific delivery can be achieved by providing the composition in a capsule, tablet or pellet which is coated with a material which dissolves in the small intestine or is degraded by the conditions in the colon.

What is claimed is:  
     
       1. A drug deliver composition for colonic delivery comprising 
       (a) a polar drug;  
       (b) an absorption promoter comprising a mixture of  
       (i) a dispersing agent, and  
       (ii) a substance selected from the group consisting of fatty acids having 6 to 16 carbon atoms, salts of fatty acids having 6 to 16 carbon atoms, and mono/diglycerides of fatty acids having fatty acids with carbon chains of 6 to 16 carbon atoms; and  
       (c) a means provided to prevent release of the polar drug and absorption promoter until the composition reaches the terminal ileum or the colon following oral administration,  
       wherein the means is a formulation selected from the group consisting of capsules, tablets, and pellets, coated with a material having a thickness between about 80 μm and 300 μm which is dissolved by the conditions found in the intestines.  
     
     
       2. The drug delivery composition of claim  1  wherein the ratio of fatty acid to dispersing agent is in the range of between about 1:10 and 10:1. 
     
     
       3. The drug delivery composition of claim  1  wherein the fatty acid is capric acid or a salt thereof. 
     
     
       4. The drug delivery composition of claim  1  wherein the dispersing agent is selected from the group consisting of polyglycolysed glycerides, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene alkyl ethers, polyoxyethylene glycol esters, and mixtures thereof. 
     
     
       5. The drug delivery composition of claim  4  wherein the polyglycolysed glyceride is a glyceryl caprylate/caprate and PEG-8 caprylate/caprate complex. 
     
     
       6. The drug delivery composition of claim  1  wherein the polar drug is selected from the group consisting of insulin, calcitonin, desmopressin, hormones, growth hormone releasing hormones, colony stimulating factors, parathyroid hormone, luteinising hormone releasing hormones, interferons, erythropoietin, bisphosphonates, antisense agents, and DNA. 
     
     
       7. The drug delivery composition of claim  1  wherein the polar drug and absorption promoter are released in the proximal colon following oral administration. 
     
     
       8. The drug delivery composition of claim  1  wherein the coating comprises a material which is redox-sensitive. 
     
     
       9. The drug delivery composition of claim  8  wherein the coating comprises an azopolymer or a disulphide polymer. 
     
     
       10. The drug delivery composition of claim  1  wherein the coating comprises a material which is degraded by enzymes or bacteria present in the colon. 
     
     
       11. The drug delivery composition of claim  1  wherein the coating comprises a material which dissolves at a pH of 5 or above. 
     
     
       12. The drug delivery composition of claim  11  wherein the coating comprises methylmethacrylate or a copolymer of methacrylic acid and methyl methacrylate. 
     
     
       13. The drug delivery composition of claim  11  wherein the coating comprises a cellulose ester. 
     
     
       14. A method for enhancing delivery of a polar drug to the colon comprising 
       incorporating the polar drug in an absorption promoter comprising a mixture of  
       (a) a dispersing agent, and  
       (b) a substance selected from the group consisting of fatty acids halving 6 to 16 carbon atoms, salts of fatty acids having 6 to 16 carbon atoms, and mono/diglycerides of medium chain fatty acids,  
       providing a means to prevent release of the polar drug and absorption promoter until the drug and absorption promoter reach the terminal ileum or the colon following oral administration wherein the means is a formulation selected from the group consisting of capsules, tablets, and pellets, coated with a material having a thickness between about 80 μm and 300 μm which is dissolved by the conditions found in the intestines.  
     
     
       15. A method of administering a polar drug to the colon of a patient in need thereof comprising administering to the patient a drug delivery composition comprising 
       (a) a polar drug;  
       (b) an absorption promoter comprising a mixture of  
       (i) a dispersing agent, and  
       (ii) a substance selected from the group consisting of fatty acids having 6 to 16 carbon atoms, salts of fatty acids having 6 to 16 carbon atoms, and mono/diglycerides of medium chain fatty acids; and  
       (c) a means provided to prevent release of the polar drug and absorption promoter until the composition reaches the terminal ileum or the colon following oral administration.  
       wherein the means is a formulation selected from the group consisting of capsules, tablets, and pellets, coated with a material having a thickness between about 80 μm and 300 μm which is dissolved by the conditions found in the intestines.  
     
     
       16. The drug delivery composition of claim  1  wherein the composition is formulated into pellets encapsulated in a capsule coated with the material which is dissolved by the conditions found in the intestines.